The cornea and sclera make up the outer tunic of the eye. Each is a connective tissue containing collagen fibrils embedded in a proteoglycan-rich extrafibrillar matrix, wherein the cornea is uniquely transparent and the sclera is totally opaque. Both tissues require strength to maintain the excess pressure within the eye and to resist external knocks and forces applied by extraocular muscles during eye movement. The mechanical strength is provided by deposition of collagen in a lamellar structure, wherein the lamellae run parallel to the surface of the tissue. The sclera as the white part of the eye is a tough connective tissue and is continuous with the cornea. Scleral collagen is, in composition and arrangement, similar to that of normal skin, with wider fibrils and much more interwoven structure than in the cornea. The sclera has no optical role other than to provide support for the retina on the back of the eye, but it has important physiological functions such as providing fluid outflow channels and mechanical functions such as maintaining an eye shape. The limbus constitutes the border between the cornea and the sclera. Changes of the collagen structure of the sclera and cornea are accompanied by a development of shortsightedness (myopia). The above-mentioned relationships are e.g. taught by K. M. Meek, Chapter 13, The Cornea and Sclera, pages 359 ﬀ. of: P. Frantzl (ed.) Collagen Structure and Mechanics, Springer 2008, ISBN: 978-0-387-73905-2.
With increasing age of a person refractive errors of the eye occur and are caused substantially by degradation of the eye tissue and in particular of the sclera and cornea. The refractive error might be called, depending on its effect, either Myopia, Hyperopia, Astigmatism or Presbyopia. Myopia is one of the most common new defective visions because of an increasing tallness of mankind resulting in an increasing length of the eyeball. A Keratoconus causing a Hyperopia, for example, is caused by a weakness of the sclera, such that the sclera and cornea are elongated in a certain circular area around the pupil. In any case the occurring weakness of the cornea and sclera is caused by the degradation of the respective collagen tissue of the eye. Conventionally the Keratoconus is either cured by a cornea transplantation or compensated by a hard contact lens. On the other hand also noninvasive treatments for a reconstitution of the cornea and/or sclera are known.
DE 10 2010 020 194 A1 discloses an ophthalmologic Laser therapy system with a Laser light source, wherein the light wavelength is adjusted to induce in the collagen tissue an energy which is just sufficient for inducing a covalent binding but which does not yet cause an ablation or the like. A photosensitizer containing agent such as Riboflavin is said to be not necessary anymore. An optical detector detects cuts in the cornea which are closed and “glued” by the Laser light treatment for stabilizing the cornea. However the light is applied over fields of the cornea or sclera and does not take any orientation of the respective collagen fibers of the tissue into account.
WO 2007 082 127 A2 discloses a combined therapy for a long lasting controlled kerato-reformation, comprising a measurement of the total corneal topography, an ablation of parts of the cornea, optionally a production of a corrective contact lens and a UVA light treatment for growing new crosslinks within the collagen tissue. For the UVA light induced growth of the new crosslinks the photosensitizer Riboflavin is applied in the form of eye drops which increase the amount of the new crosslinks in the cornea. In this way, the biomechanical rigidity or strength of the cornea is increased. The applied light has a wavelength of 365 nm and an intensity of 3 mW/cm2 over 30 minutes. However the microstructure of the collagen is not taken into account.
EP 1 2177 266 A1 by the author of the present invention discloses a Laser therapy system for rejuvenation of the skin via a combined treatment of a first UVA light treatment for collagen crosslinking and a second Laser light treatment with another light source for a subcutaneous Laser needling application. The integrated optical system allows a precise placement of the focus point or light spot, respectively, of the first UVA light and of the second Laser light treatment.
DE 10 2010 022 634 A1 discloses an ophthalmologic Laser therapy system with a pulsed Laser light source, a controllable optical system and a Hartman-Shack sensor, wherein a laser light pulse is positioned and controlled such that the energy is kept constant and at a level for a disruption of the tissue.
WO 2009 033 083 A1 gives a generic view of possible treatments and reactions of the sclera and/or cornea. Treatment of myopia and hyperopia by surgical techniques including corneal interventions, such as reshaping a surface curvature of the cornea, and of non-corneal manipulations, such as altering properties of the sclera, a ciliary muscle, zonules, or the lens, is described. Also a cutting of kerfs into portions of the sclera to improve an accommodation possibility is disclosed. However this increases the risk of infections. A generation of a low-level radiation is preferred for the treatment of the sclera and the ciliary muscle to improve a refraction of the eye, with a light energy not ablating tissue from the sclera or the ciliary muscle. In this document the effects are described rather than a controlled collagen growth within the sclera or cornea.
EP 2 108 347 A1 discloses another ophthalmologic Laser therapy system for a controlled cornea ablation, wherein a surface and thickness of the cornea are detected by an optical coherence tomography system (OCT) and a Laser light beam is controlled in a time-, energy- and space-controlled manner. Thus certain regions of the cornea with irregularities are detected via the OCR and controllably ablated by the Laser beam. The OCR imaging system has a resolution of some 10 μm in the x/y direction and 3 μm in the z direction orthogonal to the surface of the cornea. The process of detecting, controlling and generating the Laser beam happens in real time. However the process takes only an ablation of cornea tissue into account and not a growth of new tissue.
US 2012 059 439 A1 discloses an aberration control by induced new collagen crosslinking combined with a beam shaping technique. It is taught that new collagen crosslinking is used to alter a characteristic of the cornea, such as thickness or refractive index to correct wavefront aberrations. The used light wavelength is 365-370 nm with a light intensity of 3 mW/cm2. However, the UVA light is applied rather as a wide beam over an area of a certain part of the cornea and not as a pattern of a focused light beam. Also, a tightening of the outer sclera to give the eyeball a corrected shape is not mentioned.
A method for skin rejuvenation and strengthening the skin as well as the cornea and sclera in terms of better biomechanical properties such as elasticity and density is by stimulating a new crosslinking within the skin. The crosslinks between the collagen fibers and fiber bundles belong to the substantial components of the collagen tissue structure giving the skin its particular and typical biomechanical properties such as its elasticity and strength. A growth of the new crosslinks between the collagen fibers can be induced by a pretreatment of the skin with the Riboflavin containing and skin penetrating agent in combination with UVA light. The UVA light activates a process similar to a lysyl oxidase process. Lysyl oxidase is an extracellular copper enzyme that catalyzes formation of aldehydes from lysine residues in collagen and elastin precursors. The aldehydes are highly reactive, and undergo spontaneous chemical reactions with other lysyl oxidase-derived aldehyde residues, or with unmodified lysine residues. This results in crosslinking collagen and elastin, which is essential for stabilization of collagen fibrils and for the integrity and elasticity of mature elastin and, last but not least, for the skin. Complex crosslinks are formed in collagen and in elastin that differ in structure (source: Wikipedia). During crosslinking end parts of the collagen fibrils become connected with each other in a kind of covalent connection, wherein the space between the collagen fibrils becomes shorter causing a contraction of the collagen tissue in that region. In other words, if the collagen tissue is contracted in x/y direction and parallel to the skin surface the collagen tissue also grows in thickness in an orthogonal z-direction. An application of a photosensitizes agent containing e.g. Riboflavin in combination with a UVA light stimulates a process similar to the lysyl oxidase process and the crosslinking therewith.
WO 2012/158991 A2 discloses a light therapy treatment device for a controlled application of a crosslinking agent, according to the preamble of claim 1. Said device is adapted for an application of a determined amount of cross-linking agent as function of position, to achieve a growth of new cross-links in certain areas of the eye. However, the light energy is spread and not minimized for a desired growth of the new collagen cross-links.
WO 2012/145159 A1 discloses a light therapy treatment device similar to that of WO 2012/158991 A2, wherein said device is furthermore adapted for measurements of the shape cornea and for a control of the light energy taking into account a feedback signal of the growth of a corneal surface. However, the light energy is still spread and not minimized and controlled locally according to an orientation of the existing collagen fibers or fiber bundles.
However, the induction of the new crosslinks within the collagen tissue by the UVA light must also be seen in view of a toxic effect on the skin as well. Thus, the applied UVA energy has to be reduced as much as possible, such that the desired new crosslinks are generated with minimum UVA energy. Also the collagen tissue could be shaped more precisely and determined by an application of the UVA light within a focus point and by taking a microstructure of the collagen tissue into account.
For clarity reasons the eye is to be understood as a living eye. The UVA light is equivalent to UVA energy or energy density, whatever is correct in the respective sense which is apparent to a person skilled in the art. The UVA light can be a Laser light or another light.